Pushing Beyond the Central Dogma

CAMBRIDGE, MA -- Last week, a standing-room-only audience of faculty and students from Massachusetts Institute of Technology (MIT) offered rapt attention as Whitehead Institute Founding Member and former director Gerald R. Fink delivered MIT’s prestigious Killian Award Lecture.

The James R. Killian Jr. Faculty Achievement Award — the most significant recognition MIT bestows on faculty — was given to recognize Fink’s standing as a scientist who has both fundamentally changed the way researchers approach biological problems and mentored generations of scientific leaders. A pioneer in the field of genetics, Fink is the Margaret and Herman Sokol Professor in Biomedical Research and American Cancer Society Professor of Genetics in MIT’s Department of Biology.

Killian Award recipients deliver a special lecture open to the entire MIT community; and the lecturers are asked to eschew disciplinary complexity and technical jargon in discussing a topic of broad importance and compelling interest. For his topic, Fink took the deceptively simple question, What is a Gene?

The challenge in addressing that question, he noted, is that the answer that had sufficed for 50 years is obsolete. The central dogma of genetics was that a gene consists of a DNA sequence that is read into RNA to guide the formation of a protein important for cellular function. Yet, as researchers delved deeper into the genome, they found that 98 percent of DNA sequences do not code for proteins. Much of this non-coding DNA specifies only RNA and was thought to be junk.

But, Fink explained, non-coding is not the same as non-functional: We now know that RNA plays other roles than just as an intermediary on the way to protein creation. And he walked his audience through research — including seminal findings from his own lab — that has illuminated the multifaceted role RNA plays in regulating gene activity and cellular function. Indeed, scientists have found that many kinds of RNA molecules — such as microRNAs, long non-coding RNAs, and anti-sense RNAs — are involved in gene regulation.

“We’re only now beginning to visualize the importance of this formerly invisible part of the genome,” Fink noted.

Fink, apparently, views that as a challenge to be met; and despite the five decades of achievement already under his belt, he continues to make formidable contributions to science’s understanding of how the genome functions. Earlier this year, for example, he co-authored a paper in Nature that revealed a surprising and previously unrecognized role for introns, the parts of messenger RNAs that lack the instructions for making proteins and that are typically cut away and rapidly destroyed. Using yeast, the study showed that some RNA introns are not destroyed; instead they play a role in regulating growth, particularly under stressful conditions. Like so much of what was once considered “junk” DNA, the intron information would not be identified by the classical definition of the gene.

Clearly, for Fink, the process of re-defining the gene remains an active endeavor.